Description of a nationwide structure for monitoring nosocomial outbreaks of (highly resistant) microorganisms in the Netherlands: characteristics of outbreaks in 2012-2021

BACKGROUND: Before 2012, established national surveillance systems in the Netherlands were not able to provide a timely, comprehensive epidemiological view on nosocomial outbreaks. The Healthcare-associated Infections and AntiMicrobial Resistance Monitoring Group (SO-ZI/AMR) was initiated in 2012 for timely national nosocomial outbreak monitoring and risk assessment. This paper aims to describe the achievements of the SO-ZI/AMR by presenting characteristics of outbreaks reported in 2012-2021. METHODS: Hospitals and, since 2015, long-term care facilities (LTCF) were requested to report outbreaks when (1) continuity of care was threatened, or (2) transmission continued despite control measures. A multi-disciplinary expert panel (re-)assessed the public health risk of outbreaks during monthly meetings, using 5 severity phases and based on data collected via standardised questionnaires. We descriptively studied the panel's consensus-based severity classification, distribution of (highly resistant) microorganisms, and duration and size of outbreaks between April 2012 and December 2021. RESULTS: In total, 353 hospital outbreaks and 110 LTCF outbreaks were reported. Most outbreaks (hospitals: n = 309 (88%), LTCF: n = 103 (94%)) did not progress beyond phase 1 (no public health implications, outbreak expected to be controlled within two months), one hospital outbreak reached phase 4 (insufficient/ineffective response: possible public health threat, support offered). Highly resistant microorganisms (HRMO) were involved in 269 (76%) hospital and 103 (94%) LTCF outbreaks. Most outbreaks were caused by methicillin-resistant Staphylococcus aureus (MRSA; n = 93 (26%) in hospitals, n = 80 (72%) in LTCF), vancomycin-resistant Enterococcus faecium (VRE; n = 116 (33%) in hospitals, n = 2 (2%) in LTCF) and highly resistant Enterobacterales (n = 41 (12%) in hospitals, n = 20 (18%) in LTCF). Carbapenemase-producing gram-negative bacteria were involved in 32 (9.1%) hospital and five (4.5%) LTCF outbreaks. In hospitals, VRE outbreaks had the longest duration (median 2.3; range 0.0-22.8 months) and widest range of affected patients (median 9; range 2-483). CONCLUSIONS: The SO-ZI/AMR provided national insight into the characteristics of nosocomial outbreaks over the past decade. HRMO outbreaks - mostly caused by MRSA, VRE (in hospitals) and highly resistant Enterobacterales - occurred regularly, but most of them were controlled quickly and did not develop into a public health threat. The SO-ZI/AMR has become a solid monitoring body, essential to assess risks and raise awareness of potential HRMO threats

The role of platelets in sepsis

Platelets are small circulating anucleate cells that are of crucial importance in haemostasis. Over the last decade, it has become increasingly clear that platelets play an important role in inflammation and can influence both innate and adaptive immunity. Sepsis is a potentially lethal condition caused by detrimental host response to an invading pathogen. Dysbalanced immune response and activation of the coagulation system during sepsis are fundamental events leading to sepsis complications and organ failure. Platelets, being major effector cells in both haemostasis and inflammation, are involved in sepsis pathogenesis and contribute to sepsis complications. Platelets catalyse the development of hyperinflammation, disseminated intravascular coagulation and microthrombosis, and subsequently contribute to multiple organ failure. Inappropriate accumulation and activity of platelets are key events in the development of sepsis-related complications such as acute lung injury and acute kidney injury. Platelet activation readouts could serve as biomarkers for early sepsis recognition; inhibition of platelets in septic patients seems like an important target for immune-modulating therapy and appears promising based on animal models and retrospective human studie

Diagnostic value of chest x-ray in patients with suspected infection and no respiratory signs or symptoms

Suspicion of an infection without localizing signs or symptoms is a common problem. A chest x-ray (CXR) is often performed to rule out pneumonia. Our prospective cross-sectional study suggests that a CXR has no diagnostic value in patients without respiratory signs or symptoms, if a reliable medical history can be obtained

Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median of 5 × 10(9)/L or to 5 to 13 × 10(9)/L by administration of a depleting antibody in mice infected with Klebsiella via the airways. Thrombocytopenia was associated with strongly impaired survival during pneumonia-derived sepsis proportional to the extent of platelet depletion. Thrombocytopenic mice demonstrated PC-dependent enhanced bacterial growth in lungs, blood, and distant organs. Severe thrombocytopenia resulted in hemorrhage at the primary site of infection, but not in distant organs. PCs of 5 to 13 × 10(9)/L were sufficient to largely maintain hemostasis in infected lungs. Thrombocytopenia did not influence lung inflammation or neutrophil recruitment and did not attenuate local or systemic activation of coagulation or the vascular endothelium. PCs <5 × 10(9)/L even resulted in enhanced coagulation and endothelial cell activation, which coincided with increased proinflammatory cytokine levels. In accordance, low PCs in whole blood enhanced Klebsiella-induced cytokine release in vitro. These data suggest that platelets play an important role in host defense to Klebsiella pneumosepsi

Thrombocytopenia impairs host defense during murine Streptococcus pneumoniae pneumonia

Streptococcus pneumoniae is the most common causative pathogen in community-acquired pneumonia. In patients, thrombocytopenia is correlated with an adverse outcome of pneumonia. Platelets can modulate the host response to infection in several ways, that is, by facilitating clot formation, production of antimicrobial proteins, and interaction with neutrophils. We studied the effect of thrombocytopenia during murine pneumococcal pneumonia. Animal study. University research laboratory. Mice. Pneumonia was induced by intranasal inoculation of S. pneumoniae. Platelets were depleted by anti-mouse thrombocyte serum; controls received nonimmunogenic serum. In separate studies, mice were treated with the platelet P2Y12 receptor inhibitor clopidogrel or placebo. Thrombocytopenic mice (platelet counts < 1% of uninfected controls) showed a reduced survival during pneumococcal pneumonia (27% vs 75% among controls; p = 0.003), which was associated with higher bacterial loads in lungs, spleen, and blood. Thrombocytopenic mice showed enhanced coagulation activation (thrombin-antithrombin complexes) in plasma. Proinflammatory cytokine levels were higher in plasma but not in lungs of thrombocytopenic mice. Although clopidogrel treatment strongly prolonged the bleeding time, it did not impact on bacterial loads during pneumococcal pneumonia. Platelets play a protective role during pneumococcal pneumonia independent of their aggregatio

Toll-Like Receptor Signalling Is Not Involved in Platelet Response to <i>Streptococcus pneumoniae In Vitro</i> or <i>In Vivo</i>

<div><p><i>Streptococcus (S</i>.<i>) pneumoniae</i> strains vary considerably in their ability to cause invasive disease in humans, which is at least in part determined by the capsular serotype. Platelets have been implicated as sentinel cells in the circulation for host defence. One of their utensils for this function is the expression of Toll-like receptors (TLRs). We here aimed to investigate platelet response to <i>S</i>. <i>pneumoniae</i> and a role for TLRs herein. Platelets were stimulated using four serotypes of <i>S</i>. <i>pneumonia</i> including an unencapsulated mutant strain. <i>In vitro</i> aggregation and flow cytometry assays were performed using blood of healthy volunteers, or blood of TLR knock out and WT mice. For <i>in vivo</i> pneumonia experiments, platelet specific <i>Myd88</i> knockout (Plt-<i>Myd88</i>^-/-) mice were used. We found that platelet aggregation was induced by unencapsulated <i>S</i>. <i>pneumoniae</i> only. Whole blood incubation with all <i>S</i>. <i>pneumoniae</i> serotypes tested resulted in platelet degranulation and platelet-leukocyte complex formation. Platelet activation was TLR independent, as responses were not inhibited by TLR blocking antibodies, not induced by TLR agonists and were equally induced in wild-type and <i>Tlr2</i>^<i>-/-</i>, <i>Tlr4</i>^<i>-/-</i>, <i>Tlr2/4</i>^<i>-/-</i>, <i>Tlr9</i>^<i>-/-</i> and <i>Myd88</i>^<i>-/-</i> blood. Plt-<i>Myd88</i>^<i>-/-</i> and control mice displayed no differences in bacterial clearance or immune response to pneumonia by unencapsulated <i>S</i>. <i>pneumoniae</i>. In conclusion, <i>S</i>. <i>pneumoniae</i> activates platelets through a TLR-independent mechanism that is impeded by the bacterial capsule. Additionally, platelet MyD88-dependent TLR signalling is not involved in host defence to unencapsulated <i>S</i>. <i>pneumoniae in vivo</i>.</p></div